Acute viral hepatitis presenting as cytomegalovirus, hepatitis E and Epstein–Barr virus IgM antibody positive Qin Huang, Xin-Hua Li, Cuiyun Zhu, Jingjing Yan, Zhigang Song, Shuye Zhang, Yunwen Hu, Liang Chen, Yun Ling Antiviral Therapy 2015; 10.3851/IMP2991 Submission date Acceptance date Publication date
21st July 2015 30th August 2015 17th September 2015
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Publication: Antiviral Therapy; Type: Case report DOI: 10.3851/IMP2991
Case report Acute viral hepatitis presenting as cytomegalovirus, hepatitis E and Epstein–Barr virus IgM antibody positive Qin Huang1†, Xin-Hua Li2†, Cuiyun Zhu1, Jingjing Yan3, Zhigang Song4, Shuye Zhang3, Yunwen Hu4, Liang Chen5‡, Yun Ling1*‡ 1
Department of Infectious Disease, Shanghai Public Health Clinical Center Affiliated to Fudan
University, Shanghai, China 2
Department of Infectious Disease, The Third Affiliated Hospital of Sun-Yat-Sen University,
Guangzhou, China 3
Scientific Research Center, Shanghai Public Health Clinical Center Affiliated to Fudan University,
Shanghai, China 4
Department of Pathogen Diagnosis and Biosafety, Shanghai Public Health Clinical Center Affiliated to
Fudan University, Shanghai, China 5
Department of Hepatology, Shanghai Public Health Clinical Center Affiliated to Fudan University,
Shanghai, China *Corresponding author e-mail:
[email protected] †
These authors contributed equally to this work
‡
These authors contributed equally to this work
Abstract We report a case of acute CMV infection with positive HEV and EBV serology. No patients have been reported positive for IgM antibodies to all three viruses. This patient had progressively increasing titers of IgM antibody for CMV, HEV and EBV. Only CMV DNA was detectable before antiviral treatment. After antiviral treatment, the patient recovered completely. Recently at day 180 the CMV IgG test had converted to positive with CMV IgM (+), EBV IgM (-), HEV IgM (-). Our report indicates that dependence upon serology alone is unreliable in the diagnosis of acute CMV, EBV, and HEV infections. The diagnosis of CMV, HEV, and EBV should be based on a combination of clinical features, serology, and confirmatory PCR testing. Accepted 30 August 2015, published online 17 September 2015 Cytomegalovirus (CMV) is a common virus that can infect almost anyone, but it rarely produces symptoms in immunocompetent people, and is an infrequent cause for viral hepatitis [1]. Detection of specific IgM antibody (anti-CMV IgM) is widely used for Laboratory diagnosis [2]. Herein, we report a
Publication: Antiviral Therapy; Type: Case report DOI: 10.3851/IMP2991 case of acute CMV infection with positive HEV and EBV serology. This patient had progressively increasing titers of IgM antibody for CMV, HEV and EBV. Only CMV DNA was detectable before antiviral treatment. After antiviral treatment, the patient recovered completely. A 28-year-old Chinese woman presented to our hospital with fever and abnormal liver function (alanine aminotransferase, ALT 74 (7-40 U/L)). Symptoms that included high fever, malaise, myalgia, sore throat, chills and headache, had developed 2 weeks before. The temperature could be as high as 40°C at night; no rash was evident. The patient had been treated with several antibiotics, but the symptoms had not improved. She had no history of immunodeficiency or Immune-inhibitory drug use. No endocrine, metabolic or autoimmune abnormalities were found. The patient’s partner, who had shared the same food and activities, had not developed any symptoms. On admission (14 days after onset), physical examination revealed a temperature of 40°C, without skin rash or jaundice. Blood examination revealed normal white blood cell count and absolute lymphocyte count, accompanied by slightly low red blood cell and platelet counts. She had normal proportions of circulating CD3+, CD4+ and CD8+ T cells. C-reactive protein (CRP) was 28.0 (0-3.0 mg/L), lactate dehydrogenase 589 (109-245 U/L), ALT 82 (7-40 U/L), Total bilirubin (Tbil) 5.4 (0-17 umol/L), and Direct bilirubin (Dbil) 3.3 (0-5.4 umol/L). The patient had normal TSH levels and tests did not reveal anti-DNA, anti-nuclear, or anti-thyroglobulin antibodies. The HIV test was negative. Serologic testing on admission showed CMV IgM (+), CMV IgG (-), EBV IgM (+), HEV IgM (+), HEV IgG (+)(Figure 1). At the same time the test for virus in blood by polymerase chain reaction (PCR) showed detectable CMV load (DNA 2480, 0-2000 IU/mL) and negative results for EBV DNA and HEV RNA. Based on the clinical features and laboratory test results, a diagnosis of CMV acute infection was considered. The patient received ganciclovir at 5 mg/kg of body weight intravenously from day 16. The peak of body temperature had decreased on day 17, and from day 18 the patient had a normal temperature. Serologic testing was applied again at day 17. The CMV IgM, EBV IgM and HEV IgM tests were still positive, and the titer of antibodies were increasing. However, the CMV DNA was now below detectable levels. Tests for EBV DNA and HEV RNA were still negative. The patient fully recovered and was discharged from hospital at day 27 after onset. The patient was followed up for more than 6 months, without recurrence of symptoms. The CMV IgM, EBV IgM and HEV-IgM tests were still positive at day 47. Recently at day 180 the CMV IgG test had converted to positive with CMV IgM (+), EBV IgM (-), HEV IgM (-) Infectious mononucleosis can present as elevated IgM titres to both CMV and EBV [3]. HEV infected patients can show false reactivity to CMV or EBV according to diverse sources of data [4–6]. A high degree of EBV and CMV cross reactivity was reported, with 33.3% and 24.2% of HEV IgM positive samples also testing positive for EBV and CMV IgM [6], respectively. However, no patients have been reported positive for IgM antibodies to all three viruses. Polyclonal stimulation of memory B-cell clones and immunological cross-reactivity might be giving problems when IgM tests are positive for all three [6]. Overall, a high level of HEV, EBV and CMV IgM cross-reactivity has been reported, indicating that dependence upon serology alone is unreliable in the diagnosis of acute CMV, EBV, and HEV infections. The diagnosis of CMV, HEV, and EBV should be based on a combination of clinical features, serology, and confirmatory PCR testing.
Publication: Antiviral Therapy; Type: Case report DOI: 10.3851/IMP2991 Acknowledgment statement We thank Huijun Mao, Jinbiao Peng and Daihong Chen for expert technical assistance. This work was supported by grants from SHAPHC(KSF0640 and RCJJP19).
Disclosure statement The authors have no conflict of interest to declare.
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Figure legend Figure 1. The fold changes of CMV, HEV and EBV-antibody titres after disease onset. Each symbol represents a single result from the patient: CMV-IgM (red filled circles), CMV-IgG (red empty circles), HEV-IgM (blue filled triangles), HEV-IgG (blue empty triangles) or EBV-IgM (black filled squares). All titre values were divided by the Lower Limit of Detection (LLD), and over 1 means positive.
Figure 1
CMV-IgM CMV-IgG
Folds
11
EBV-IgM HEV-IgM HEV-IgG
6
1 0
50
100
150
Days after onset
200
