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Schattner A. The Wide Spectrum of Presentations of Cytomegalovirus Infection in Immunocompetent Hosts: An Exhaustive Narrative Review. Pathogens 2024; 13:667. [PMID: 39204267 PMCID: PMC11357360 DOI: 10.3390/pathogens13080667] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2024] [Revised: 07/09/2024] [Accepted: 07/26/2024] [Indexed: 09/03/2024] Open
Abstract
CMV is a ubiquitous DNA virus that establishes infection and results in 40-100% seropositivity. Viral replication occurs following an acquired primary infection (or reinfection) or by the reactivation of life-long latency. In immunocompetent patients, CMV infection is mostly asymptomatic or mild and self-limited. However, an extensive review of the literature published up to April 2024 reveals that despite immunocompetence, CMV can cause a very large variety of clinical syndromes in any part of the gastrointestinal tract (the most common pattern), the central or peripheral nervous system, and the eyes, as well as hematological, pulmonary, cardiac, and cutaneous disease. Not uncommonly, more than one system is involved, and though the disease is often self-limited, treatment with intravenous ganciclovir or oral valganciclovir may be required, and in isolated cases, fatalities may occur. Thus, a potential CMV infection should be considered in the differential of myriad syndromes in non-immunocompromised patients. Associated systemic symptoms (fever, sweats, and weight loss), lymphocytosis, and hepatitis are not uncommon and can be a useful clue. Some populations, such as critically ill patients in intensive care, pregnant women, elderly patients, and those with inflammatory bowel disease, may be more susceptible. Moreover, the potential of past, latent CMV infection (i.e., CMV seropositivity) to be associated with significant cardiovascular morbidity and all-cause mortality years later is intriguing and requires further study. All these data indicate the outstanding importance of developing a vaccine against CMV, which hopefully will become available in the foreseeable future. Meanwhile, a solid diagnosis of active CMV infection can be quickly established (or ruled out) by widely available serology tests and PCR amplification, and clinicians in all disciplines need to be more aware of the diverse guises of CMV infection and remember to consider it in any host, including an immunocompetent one.
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Affiliation(s)
- Ami Schattner
- The Faculty of Medicine, Hebrew University Hadassah Medical School, Ein Kerem, Jerusalem 91120, Israel
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2
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Yu X, Wang M, Kong Q. Viral pancreatitis: research advances and mechanisms. Front Microbiol 2024; 14:1326837. [PMID: 38420214 PMCID: PMC10901110 DOI: 10.3389/fmicb.2023.1326837] [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: 10/24/2023] [Accepted: 12/20/2023] [Indexed: 03/02/2024] Open
Abstract
Acute pancreatitis is caused by trypsinogen activation in acinar cells caused by various injury forms (gallstone, high triglycerides, alcohol, etc.). Viral pancreatitis is a clinically rare disease type, which is easily neglected by clinicians and causes serious adverse consequences. Viral pancreatitis involves the entry of viruses into pancreatic cells, triggering inflammation, immune response activation, and enzymatic autodigestion, leading to tissue damage and potential complications. At present, there are few available reports on viral pancreatitis, most of which are case reports. This review brings attention to clinicians by describing the incidence of viral pancreatitis to enhance clinical understanding and patient care.
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Affiliation(s)
- Xianqiang Yu
- Medical School, Qingdao University, Qingdao, China
| | - Minchao Wang
- Lishui Second People's Hospital Affiliated to Wenzhou Medical University, Lishui, China
| | - Qingming Kong
- School of Basic Medicine and Forensics, Key Laboratory of Bio-tech Vaccine of Zhejiang Province, Engineering Research Center of Novel Vaccine of Zhejiang Province, Hangzhou Medical College, Hangzhou, China
- Key Laboratory of Biomarkers and In Vitro Diagnosis Translation of Zhejiang province, School of Laboratory Medicine and Bioengineering, Hangzhou Medical College, Hangzhou, China
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Sticova E, Fabian O. Morphological aspects of small-duct cholangiopathies: A minireview. World J Hepatol 2023; 15:538-553. [PMID: 37206655 PMCID: PMC10190694 DOI: 10.4254/wjh.v15.i4.538] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Revised: 02/03/2023] [Accepted: 03/22/2023] [Indexed: 04/20/2023] Open
Abstract
The biliary system consists of intrahepatic and extrahepatic bile ducts lined by biliary epithelial cells (cholangiocytes). Bile ducts and cholangiocytes are affected by a variety of disorders called cholangiopathies, which differ in aetiology, pathogenesis, and morphology. Classification of cholangiopathies is complex and reflects pathogenic mechanisms (immune-mediated, genetic, drug- and toxin-induced, ischaemic, infectious, neoplastic), predominant morphological patterns of biliary injury (suppurative and non-suppurative cholangitis, cholangiopathy), and specific segments of the biliary tree affected by the disease process. While the involvement of large extrahepatic and intrahepatic bile ducts is typically visualised using radiology imaging, histopathological examination of liver tissue obtained by percutaneous liver biopsy still plays an important role in the diagnosis of cholangiopathies affecting the small intrahepatic bile ducts. To increase the diagnostic yield of a liver biopsy and determine the optimal therapeutic approach, the referring clinician is tasked with interpreting the results of histopathological examination. This requires knowledge and understanding of basic morphological patterns of hepatobiliary injury and an ability to correlate microscopic findings with results obtained by imaging and laboratory methods. This minireview describes the morphological aspects of small-duct cholangiopathies pertaining to the diagnostic process.
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Affiliation(s)
- Eva Sticova
- Clinical and Transplant Pathology Centre, Institute for Clinical and Experimental Medicine, Prague 14021, Czech Republic
- Department of Pathology, The Third Faculty of Medicine, Charles University and University Hospital Kralovske Vinohrady, Prague 10000, Czech Republic
| | - Ondrej Fabian
- Clinical and Transplant Pathology Centre, Institute for Clinical and Experimental Medicine, Prague 14021, Czech Republic
- Department of Pathology and Molecular Medicine, The Third faculty of Medicine, Charles University and Thomayer University Hospital, Prague 14059, Czech Republic
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Beyhan E, Erol Fenercioğlu Ö, Şahin R, Baloğlu MC, Çermik TF. 18F-FDG PET/CT Findings in HIV-Positive Patient With Primary Pancreas Lymphoma and CMV Pancreatitis. Clin Nucl Med 2022; 47:e393-e394. [PMID: 35195582 DOI: 10.1097/rlu.0000000000004109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
ABSTRACT A 35-year-old HIV-positive man with abdominal pain was referred to 18F-FDG PET/CT for metabolic characterization of mass in pancreas. PET/CT images showed intense FDG uptake in head of the pancreas, as well as diffuse moderate uptake throughout body and tail of the pancreas. Histopathological results revealed Epstein-Barr virus (EBV) associated large B-cell lymphoma and pancreatitis caused by cytomegalovirus.
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Affiliation(s)
- Ediz Beyhan
- From the Clinic of Nuclear Medicine, Istanbul Training and Research Hospital, Istanbul, Turkey
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Alibegovic E, Kurtcehajic A, Ilic B, Hujdurovic A, Smajic E, Habibovic A, Perkunic D. Cytomegalovirus Cholangiopathy in an Immunocompetent Patient: A Case Report and Literature Review. Case Reports Hepatol 2021; 2021:2420668. [PMID: 34804619 PMCID: PMC8598330 DOI: 10.1155/2021/2420668] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2021] [Revised: 10/12/2021] [Accepted: 10/26/2021] [Indexed: 12/07/2022] Open
Abstract
A 37-year-old man presented with jaundice, upper right quadrant pain, and intermittent fever with chills. Laboratory assessment showed biliary stasis, with total bilirubin of 203 µmol/L (2-20), conjugated bilirubin of 105 µmol/L, and alkaline phosphatase of 556 U/L (30-120). Markers for hepatitis A-E viruses were negative. Serology assessment for rubeola, herpes simplex virus, Epstein-Barr virus, and Toxoplasma gondii showed negative IgM antibodies. HIV serology status was negative. For cytomegalovirus, both types of antibodies (IgM and IgG) were positive, with an IgM level >300 U/mL. pp65 antigen was also detected as well as CMV DNA. Diagnostic imaging of the abdomen except the dilated common bile duct showed a normal appearance of the gallbladder, liver, pancreas, spleen, and both kidneys. To our knowledge, cytomegalovirus cholangiopathy in the absence of any other underlying disease has not been reported. Therefore, the presence of cholangiopathy in our patient is interesting from an imaging, laboratory, and clinical point of view.
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Affiliation(s)
- Ervin Alibegovic
- Department of Gastroenterology and Hepatology, University Clinical Center Tuzla, Tuzla 75000, Bosnia and Herzegovina
- Medical Faculty, University of Tuzla, Tuzla 75000, Bosnia and Herzegovina
| | - Admir Kurtcehajic
- Medical Faculty, University of Tuzla, Tuzla 75000, Bosnia and Herzegovina
- Department of Internal Medicine, Medical Center “Plava Poliklinika”, Plava Medical Group, Tuzla 75000, Bosnia and Herzegovina
| | - Boris Ilic
- Department of Internal Medicine, Medical Center “Plava Poliklinika”, Plava Medical Group, Tuzla 75000, Bosnia and Herzegovina
| | - Ahmed Hujdurovic
- Department of Internal Medicine, Medical Center “Plava Poliklinika”, Plava Medical Group, Tuzla 75000, Bosnia and Herzegovina
| | - Edinka Smajic
- Department of Radiology, Medical Center “Plava Poliklinika”, Plava Medical Group, Tuzla 75000, Bosnia and Herzegovina
| | - Amar Habibovic
- Department of Gastroenterology and Hepatology, University Clinical Center Tuzla, Tuzla 75000, Bosnia and Herzegovina
| | - Darja Perkunic
- Department of Biochemistry, Medical Center “Plava Poliklinika”, Plava Medical Group, Tuzla 75000, Bosnia and Herzegovina
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Pötter-Lang S, Ba-Ssalamah A, Bastati N, Messner A, Kristic A, Ambros R, Herold A, Hodge JC, Trauner M. Modern imaging of cholangitis. Br J Radiol 2021; 94:20210417. [PMID: 34233488 PMCID: PMC9327751 DOI: 10.1259/bjr.20210417] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Revised: 06/09/2021] [Accepted: 06/21/2021] [Indexed: 12/07/2022] Open
Abstract
Cholangitis refers to inflammation of the bile ducts with or without accompanying infection. When intermittent or persistent inflammation lasts 6 months or more, the condition is classified as chronic cholangitis. Otherwise, it is considered an acute cholangitis. Cholangitis can also be classified according to the inciting agent, e.g. complete mechanical obstruction, which is the leading cause of acute cholangitis, longstanding partial mechanical blockage, or immune-mediated bile duct damage that results in chronic cholangitis.The work-up for cholangitis is based upon medical history, clinical presentation, and initial laboratory tests. Whereas ultrasound is the first-line imaging modality used to identify bile duct dilatation in patients with colicky abdominal pain, cross-sectional imaging is preferable when symptoms cannot be primarily localised to the hepatobiliary system. CT is very useful in oncologic, trauma, or postoperative patients. Otherwise, magnetic resonance cholangiopancreatography is the method of choice to diagnose acute and chronic biliary disorders, providing an excellent anatomic overview and, if gadoxetic acid is injected, simultaneously delivering morphological and functional information about the hepatobiliary system. If brush cytology, biopsy, assessment of the prepapillary common bile duct, stricture dilatation, or stenting is necessary, then endoscopic ultrasound and/or retrograde cholangiography are performed. Finally, when the pathologic duct is inaccessible from the duodenum or stomach, percutaneous transhepatic cholangiography is an option. The pace of the work-up depends upon the severity of cholestasis on presentation. Whereas sepsis, hypotension, and/or Charcot's triad warrant immediate investigation and management, chronic cholestasis can be electively evaluated.This overview article will cover the common cholangitides, emphasising our clinical experience with the chronic cholestatic liver diseases.
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Affiliation(s)
- Sarah Pötter-Lang
- Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria
| | - Ahmed Ba-Ssalamah
- Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria
| | - Nina Bastati
- Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria
| | - Alina Messner
- Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria
| | - Antonia Kristic
- Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria
| | - Raphael Ambros
- Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria
| | - Alexander Herold
- Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria
| | - Jacqueline C. Hodge
- Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria
| | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
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Simons-Linares CR, Imam Z, Chahal P. Viral-Attributed Acute Pancreatitis: A Systematic Review. Dig Dis Sci 2021; 66:2162-2172. [PMID: 32789532 DOI: 10.1007/s10620-020-06531-9] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Accepted: 07/31/2020] [Indexed: 01/18/2023]
Abstract
Infectious etiologies are rare cause of acute pancreatitis (AP). We sought to investigate the frequency of viral-attributed AP (VIAP) and describe its natural course and clinical features. Comprehensive review of PubMed and EMBASE in English until December 31, 2019, was performed. AP diagnosis and severity were defined per the Revised Atlanta Classification. Viral infections were diagnosed by serology and/or histology. A diagnosis of viral infection, with a concurrent AP diagnosis, a temporal resolution of both entities, and the attempt to exclude the most common etiologies of AP defined VIAP. Two independent reviewers reviewed eligible publications. Bias risk was assessed with the Murad tool. A total of 209 cases identified in 128 publications met inclusion criteria. Mean age was 38.9 ± 1.28 years. Male-to-female ratio was 2.2:1, and 28% of patients were immunocompromised. Viral hepatitis (A, B, C, D and E) was the most common virus and accounted for 34.4% of cases, followed by coxsackie and echoviruses (14.8%), hemorrhagic fever viruses (12.4%), CMV (12.0%), VZV (10.5%), mumps and measles (3.8%), primary HIV infection (3.8%), HSV (1.9%), EBV (1.9%), and the remainder of cases (2.9%) attributed to adenovirus, influenza H1N1, and multiple viruses. Severity of AP was: 43.1% mild, 11.7% moderately severe, 32.4% severe. Death occurred in 42 (20.1%) patients. A significant portion of VIAP patients were immunocompromised (28.0%) and accounted for 71.4% of mortality cases. Mortality was higher than that reported for AP from other etiologies in the literature.
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Affiliation(s)
- C Roberto Simons-Linares
- Gastroenterology and Hepatology Department, Digestive Disease Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.
| | - Zaid Imam
- Department of Internal Medicine, William Beaumont Hospital, Royal Oak, MI, USA
| | - Prabhleen Chahal
- Gastroenterology and Hepatology Department, Digestive Disease Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA
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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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9
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Imam Z, Simons-Linares CR, Chahal P. Infectious causes of acute pancreatitis: A systematic review. Pancreatology 2020; 20:1312-1322. [PMID: 32938554 DOI: 10.1016/j.pan.2020.08.018] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 08/21/2020] [Accepted: 08/24/2020] [Indexed: 01/18/2023]
Abstract
BACKGROUND Infectious etiologies of acute pancreatitis (AP) are rare and include viruses, bacteria, mycobacteria, parasites, and fungi. We aimed to conduct a comprehensive review on infectious etiologies of AP analyzing the frequency, clinical features, and outcomes of individuals presenting with this condition. METHODS Eligible articles reporting on AP attributed to infectious etiologies were included. A comprehensive literature search of PubMed from time of inception and until September 6,2019 was performed using all relevant MeSH (medical subject heading) keywords. Articles were assessed for eligibility and independently reviewed by two reviewers for clinical features of AP, local complications, and mortality. Methodological quality of included studies was evaluated using the Murad tool. RESULTS A total of 212 articles were included, of which 168 (79.2%) were at high risk of bias. 320 cases of AP were identified. Viruses were the leading etiology of infection attributed AP (65.3%) followed by helminths (19.1%), and bacteria (12.5%). Protozoa, mycobacteria, and fungi accounted for the remaining 3.1% of cases. Mean age was 40.5 ± 18.4 years and M:F ratio was 1.94:1. Mortality occurred in 50 patients. Mortality rate was higher in the virus attributed AP patients than AP from other infectious etiologies (21.8% vs. 7.0%, p < 0.0005). INTERPRETATION Literature quality on infection attributed AP is limited. Virus attributed AP appears to carry a higher mortality than other etiologies of infection attributed AP.
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Affiliation(s)
- Zaid Imam
- Department of Internal Medicine, William Beaumont Hospital, Royal Oak, MI, USA
| | - C Roberto Simons-Linares
- Department of Gastroenterology, Hepatology, and Nutrition; Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA.
| | - Prabhleen Chahal
- Department of Gastroenterology, Hepatology, and Nutrition; Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
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Saeed MI, Stephens R, Nwogbo O, Gani IY, Kapoor R, Doroodchi A. Cytomegalovirus pancreatitis in an immunocompetent patient. IDCases 2020; 22:e00932. [PMID: 33299793 PMCID: PMC7708617 DOI: 10.1016/j.idcr.2020.e00932] [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: 06/01/2020] [Revised: 08/11/2020] [Accepted: 08/12/2020] [Indexed: 11/19/2022] Open
Abstract
Cytomegalovirus (CMV) is a double-stranded DNA virus, which infects a large portion of the adult population. In immunocompetent patients, it typically is asymptomatic or manifests as mild and self-limiting flu-like illness symptoms, whereas in immunocompromised patients, CMV can cause significant disease. Herein we report an unusual case of CMV pancreatitis in an immunocompetent 75-year-old female. Patient developed severe significant pancreatic necrosis that failed non-operative management, and ultimately underwent pancreatic necrosectomy. Later on, she developed three spontaneous gastric perforations. The first two perforations were managed operatively, but after the third perforation family decided not to undergo another operation. The CMV pancreatitis diagnosis was based on pancreatic histopathology and confirms by a prompt response to ganciclovir. Patient was promptly started on intravenous (IV) ganciclovir which resulted in clinical recovery and she remained asymptomatic more than one-year post op. This is a rare case of CMV pancreatitis with gastric perforations in an immunocompetent patient. High degree of suspicion and appropriate treatment are important for such clinical scenarios.
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Key Words
- ALT, alanine transferase
- AST, aspartate transferase
- BMI, body mass Index
- CKD, chronic kidney disease
- CMV, cytomegalovirus
- CT, computed tomography
- Cytomegalovirus
- DIC, disseminated intravascular coagulation
- EBV, Epstein Barr virus
- EGD, esophagogastroduodenoscopy
- GI, gastrointestinal
- Ganciclovir
- Gastric perforation
- ICU, intensive care unit
- OR, operating room
- PCR, polymerase chain reaction
- POD, post-operative day
- Pancreatic necrosis
- Pancreatitis
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Affiliation(s)
- Muhammad I. Saeed
- Division of Transplant Surgery, Department of Surgery, Augusta University Medical Center, Augusta, GA, United States
| | - Rachel Stephens
- Department of Pharmacy, Augusta University Medical Center, Augusta, GA, United States
| | - Okechukwu Nwogbo
- Department of Pathology, Augusta University Medical Center, Augusta, GA, United States
| | - Imran Y. Gani
- Division of Nephrology, Hypertension and Transplant Medicine Department of Medicine, Augusta University Medical Center, Augusta, GA, United States
| | - Rajan Kapoor
- Division of Nephrology, Hypertension and Transplant Medicine Department of Medicine, Augusta University Medical Center, Augusta, GA, United States
| | - Atbin Doroodchi
- Division of Transplant Surgery, Department of Surgery, Augusta University Medical Center, Augusta, GA, United States
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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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12
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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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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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Low doses of CMV induce autoimmune-mediated and inflammatory responses in bile duct epithelia of regulatory T cell-depleted neonatal mice. J Transl Med 2015; 95:180-92. [PMID: 25531565 DOI: 10.1038/labinvest.2014.148] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2014] [Revised: 09/21/2014] [Accepted: 10/31/2014] [Indexed: 12/21/2022] Open
Abstract
Recent studies have indicated that perinatal infection with cytomegalovirus (CMV) may promote bile duct damage in biliary atresia (BA) and that the decreased regulatory T cell (Treg) percentage associated with BA may further amplify the bile duct damage. Although a majority of BA patients have had previous CMV infections and lower percentages of Tregs, it is unknown whether an initial exposure to a low dose of CMV could induce exaggerated and progressive biliary injury. A Treg-depleted neonatal mouse was infected with low-dose CMV (LD-CMV) as a model to study BA patients. LD-CMV infection in Treg-depleted mice induced extensive inflammation in both the intrahepatic and extrahepatic bile ducts, accompanied with injury to and atresia of intrahepatic bile ducts and partial obstruction of the extrahepatic bile ducts. Serum total and direct bilirubin amounts were also elevated. Evidence for the involvement of cellular and humoral autoimmune responses in LD-CMV-infection of Treg-depleted mice was also obtained through detection of increased percentages of CD3 and CD8 mononuclear cells and serum autoantibodies reactive to bile duct epithelial proteins, one of which was identified as α-enolase. Depletion of Tregs that can lead to the decreased inhibition of aberrantly activated hepatic T-lymphocytes and generation of autoantibodies may lead to further injury. Increased hepatic expression of Th1-related genes (TNF-α), IFN-γ-activated genes (STAT-1) and Th1 cytokines (TNF-α, lymphotactin, IL-12p40 and MIP -1γ) were also identified. In conclusion, autoimmune-mediated and inflammatory responses induced by LD-CMV infection in Treg-depleted mice results in increased intrahepatic and extrahepatic bile duct injury and contributed to disease progression.
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Oppenheimer AP, Koh C, McLaughlin M, Williamson JC, Norton TD, Laudadio J, Heller T, Kleiner DE, High KP, Morse CG. Vanishing bile duct syndrome in human immunodeficiency virus infected adults: A report of two cases. World J Gastroenterol 2013; 19:115-21. [PMID: 23326172 PMCID: PMC3542762 DOI: 10.3748/wjg.v19.i1.115] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2012] [Revised: 07/02/2012] [Accepted: 08/03/2012] [Indexed: 02/06/2023] Open
Abstract
Vanishing bile duct syndrome (VBDS) is a group of rare disorders characterized by ductopenia, the progressive destruction and disappearance of intrahepatic bile ducts leading to cholestasis. Described in association with medications, autoimmune disorders, cancer, transplantation, and infections, the specific mechanisms of disease are not known. To date, only 4 cases of VBDS have been reported in human immunodeficiency virus (HIV) infected patients. We report 2 additional cases of HIV-associated VBDS and review the features common to the HIV-associated cases. Presentation includes hyperbilirubinemia, normal liver imaging, and negative viral and autoimmune hepatitis studies. In HIV-infected subjects, VBDS occurred at a range of CD4+ T-cell counts, in some cases following initiation or change in antiretroviral therapy. Lymphoma was associated with two cases; nevirapine, antibiotics, and viral co-infection were suggested as etiologies in the other cases. In HIV-positive patients with progressive cholestasis, early identification of VBDS and referral for transplantation may improve outcomes.
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Abstract
Cytomegalovirus (CMV) infection is common worldwide, but the majority are asymptomatic. However, during initial infection or reactivation, CMV can cause tissue-invasive end-organ damage including in the gastrointestinal tract, especially in immunocompromised individuals. Gastrointestinal CMV disease can present with myriad of symptoms and be highly variable endoscopically. In this article we review the manifestations of CMV infection within the luminal gastrointestinal tract and discuss the options for diagnosis and management.
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Affiliation(s)
- David M You
- Department of Gastroenterology, Naval Medical Center, San Diego, CA 92134, USA.
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Brindley SM, Lanham AM, Karrer FM, Tucker RM, Fontenot AP, Mack CL. Cytomegalovirus-specific T-cell reactivity in biliary atresia at the time of diagnosis is associated with deficits in regulatory T cells. Hepatology 2012; 55:1130-8. [PMID: 22105891 PMCID: PMC3319336 DOI: 10.1002/hep.24807] [Citation(s) in RCA: 80] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
UNLABELLED Biliary atresia (BA) is a progressive, inflammatory cholangiopathy that culminates in fibrosis of extrahepatic and intrahepatic bile ducts. A leading theory on the pathogenesis of BA is that the bile duct damage is initiated by a virus infection, followed by a bile duct-targeted autoimmune response. One mechanism of autoimmunity entails a diminished number or function of regulatory T cells (Tregs). The aim of this study was to identify potential virus-specific liver T cells from infants with BA at the time of diagnosis, implicating the virus involved in early bile duct damage. A subaim was to determine if the presence of virus infection was associated with quantitative changes in Tregs. Liver T cells from BA and control patients were cultured with antigen-presenting cells in the presence of a variety of viral or control proteins. 56% of BA patients had significant increases in interferon-gamma-producing liver T cells in response to cytomegalovirus (CMV), compared with minimal BA responses to other viruses or the control group CMV response. In addition, a positive correlation between BA plasma CMV immunoglobulin M (IgM) and liver T-cell CMV reactivity was identified. Investigation of peripheral blood Tregs revealed significant deficits in Treg frequencies in BA compared with controls, with marked deficits in those BA patients who were positive for CMV. CONCLUSION Liver T-cell responses to CMV were identified in the majority of BA patients at diagnosis, suggesting perinatal CMV infection as a plausible initiator of bile duct damage. Deficiency of Tregs in BA implies decreased inhibition of inflammation and autoreactivity, potentially allowing for exaggerated bile duct injury.
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Affiliation(s)
- Stephen M. Brindley
- Division of Allergy & Clinical Immunology, University of Colorado Denver School of Medicine, Aurora, Colorado
| | - Allison M. Lanham
- Division of Allergy & Clinical Immunology, University of Colorado Denver School of Medicine, Aurora, Colorado
| | - Frederick M. Karrer
- Division of Pediatric Gastroenterology, Hepatology & Nutrition, Digestive Health Institute, Children’s Hospital Colorado, Aurora, Colorado
| | - Rebecca M. Tucker
- Division of Allergy & Clinical Immunology, University of Colorado Denver School of Medicine, Aurora, Colorado
| | - Andrew P. Fontenot
- Division of Allergy & Clinical Immunology, University of Colorado Denver School of Medicine, Aurora, Colorado
| | - Cara L. Mack
- Division of Allergy & Clinical Immunology, University of Colorado Denver School of Medicine, Aurora, Colorado,Division of Pediatric Gastroenterology, Hepatology & Nutrition, Digestive Health Institute, Children’s Hospital Colorado, Aurora, Colorado
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Catalano OA, Sahani DV, Forcione DG, Czermak B, Liu CH, Soricelli A, Arellano RS, Muller PR, Hahn PF. Biliary Infections: Spectrum of Imaging Findings and Management. Radiographics 2009; 29:2059-80. [DOI: 10.1148/rg.297095051] [Citation(s) in RCA: 81] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
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Wu J, Yu P, Hu Z, Zheng S. Statins can be the potential therapeutic agents for reducing infection evoked cholangiopathy after liver transplantation? Med Hypotheses 2007; 70:277-280. [PMID: 17681704 DOI: 10.1016/j.mehy.2007.06.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2007] [Accepted: 06/06/2007] [Indexed: 11/23/2022]
Abstract
Biliary infection, including bacteria and cytomegalovirus (CMV), can induce inflammatory response and lead to bile duct damage after liver transplantation. This process may involve a major class of pattern recognition receptors-TLRs (Toll-like receptors). Stimulation of these receptors by pathogens (CMV, bacteria, etc.) in bile duct can induce the secretion of a series of cytokines/chemokines mainly via a TLR-2/4-MyD88-dependent pathway. Strategies for prevention and treatment of biliary infection, such as selective digestive decontamination (SDD) and preemptive therapy with gancyclovir and antibiotics are not so satisfactory. Statin, a HMG-CoA reductase inhibitor, have special anti-inflammatory abilities. They can inhibit the expression of TLR-4 and TLR-2, and block the signaling pathways of LPS (TLR-2/4), virus-encoded envelope proteins (TLR-2) and HSP70 (TLR-2/4), This process can lead to a reduction of effector cytokines/chemokines. In addition, statins can suppress the replication of CMV by reducing NF-kappaB binding activity. We hypothesized that statins can be useful for reducing infection evoked cholangiopathy after liver transplantation. We provide reliable evidence supporting the hypothesis and offer proposals for future application.
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Affiliation(s)
- Jian Wu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, PR China
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Abstract
Cytomegalovirus enteritis is most usually associated with patients positive for human immunodeficiency virus or immunosuppressed transplant patients. The gastrointestinal tract may be affected anywhere from the esophagus to the colon, but the small bowel involvement is rare. We report a case of cytomegalovirus ileitis in an immunocompetent adult, which was confirmed by histopathologic findings through colonoscopic biopsy.
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Affiliation(s)
- Kum Hei Ryu
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea.
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