Cytomegalovirus Related Hepatitis and Meningoencephalitis in an Immunocompetent Individual  

Indrajeet  Kumar  Tiwary , Avijit  Das , Mahesh  Kumar  Goenka
Institute of Gastrosciences, Apollo Gleneagles Hospital Kolkata, India
Author    Correspondence author
International Journal of Clinical Case Reports, 2016, Vol. 6, No. 4   doi: 10.5376/ijccr.2016.06.0004
Received: 24 Oct., 2015    Accepted: 22 Dec., 2015    Published: 29 Dec., 2015
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Indrajeet Kumar Tiwary, Avijit Das, Mahesh Kumar Goenka, 2016, Cytomegalovirus Related Hepatitis and Meningoencephalitis in an Immunocompetent Individual, International Journal of Clinical Case Reports, 6(4) 1-3 (doi: 10.5376/ijccr.2016.06.0004)
 

Abstract

Cytomegalovirus (CMV) is usually considered as an important pathogen in  advanced HIV infection especially with CD4 count <50 cells/microliter and it also appears to be most common organism complicating organ transplantation. Severe infection is uncommon in immunocompetent individuals. We reported such a case in our institution which run a course of acute viral hepatitis and acute meningoencephalitis with positive serology for CMV IgM and CMV DNA without any evidence of overt immunosupression. He was treated successfully with anti viral therapy.

Keywords
Cytomegalovirus; Hepatitis; Meningoencephalitis

Introduction
CMVs are ubiquitous beta herpesviruses that infect animals as well as humans. Primary infection with human cytomegalovirus (HCMV) is followed by persistence of the virus in a latent form. It causes severe disease in immunocompromised patients, either via reactivation of latent CMV infection or via acquisition of primary CMV infection. Clinical syndromes that may be observed in this setting include encephalitis, pneumonitis, hepatitis, uveitis, retinitis, colitis, and graft rejection (Petros et al., 2008). There are few reports of severe or prolonged symptomatic infection in immunocompetent patients (Wreghitt et al., 2003). Seroprevalence for CMV worldwide ranges from 60%~100% (Staras et al., 2006). The prevalence of asymptomatic CMV infection, marked with IgG antibodies, ranges from 40% to 100% throughout the world, with highest rates observed in Asia and Africa (Ho, 1990). Symptomatic CMV infection in non-immunocompromised hosts has traditionally been considered to have a benign, self-limited course. Gastrointestinal involvement with CMV in the immunocompetent host, although rare, but can cause significant morbidity and mortality (Salik and Mohsen, 2015). In addition to involvement of gastrointestinal tract, isolated cases of CMV in immunocompetent individuals have been reported to cause encephalitis, Guillain-Barre syndrome, transverse myelitis, anterior uveitis and pneumonitis (Eddleston et al., 1997; Giobbia et al., 1999; Chee et al., 2008; Orlikowski et al., 2011; Grilli et al., 2012).

Case Report
A 53 years old non-diabetic male from rural areas of West Bengal was admitted with the history of high grade fever with chill and rigor for 10 days, jaundice for 3 days and altered sensorium for 1 day. Initially he consulted his physician but there was no clue despite doing routine blood investigations and was then shifted to our institution. He was observed in our emergency room in obtunded condition following one episode of seizure with arterial blood gas analysis showed severe metabolic acidosis and hypoxemia. He was immediately intubated and put on mechanical ventilatory support. Blood examination revealed leucocytosis, renal impairment along with deranged liver function tests (total bilirubin-9.9 mg/dl and direct bilirubin 6.3 mg/dl; SGOT/SGPT 151/127). All viral hepatitis markers (A, B, C, E), leptospira, malaria parasite, Typhi Dot M, dengue and serology for HIV 1 and 2 were negative. Sepsis was excluded by culture from blood, urine and sputum. Chest X-ray was normal. Contrast Enhanced Computed Tomography (CT) scan of whole abdomen, CT scan of brain, Electro encephalogram were done but were noncontributory. Cerebrospinal fluid (CSF) analysis showed total cell count – 60 cells per cubic mm (neutrophil 2%, lymphocyte 98%), protein-93 mg/dl, sugar-84 mg/dl, Adenosine deaminase (ADA) -7, no fungus or fungal element seen in smear, culture was sterile and TB PCR (polymerase chain reaction for tuberculosis), DNA for HSV 1,2 were negative in CSF. In view of his clinical presentation and CSF study, serology for CMV IgM (Chemiluminescent microparticle immunoassay, Architect, Abott) was sent which turned out to be positive. CMV IgG was however negative. Eye examination was within normal limits. Blood plasma for CMV DNA (Real time Polymerase Chain Reaction, Qiagen, GmbH) was positive with a load of >3 000 copies/mL. We treated him with injection Ganciclovir, 5 mg/kg body weight twice daily for a period of 2 weeks as per Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected and Adolescents Adults (http://aidsinfo.nih.gov/guidelines on 9/28/2015) along with other supportive measures. Later on, he was weaned off from mechanical ventilator and metabolic acidosis was corrected, renal and liver functions parameters improved. He became afebrile and sensorium improved. He was discharged in a hemodynamically stable condition with advice for oral Val ganciclovir 900 mg once daily which was continued for 7 days. CMV DNA repeated 3 weeks later was not detectable.

Discussion
Although CMV has a worldwide distribution, it is more common in developing countries (Chakravarty et al., 2005). Seroprevalence varies greatly with a variety of epidemiological factors.In different parts of India, serological surveys have shown 80-90% prevalence of CMV IgG antibodies in women of childbearing age. Risk of seroconversion during pregnancy averages 2.0%~2.5% (Chakravarti et al., 2009). A study by Pal et al. from Chandigarh showed 100% seropositivity for CMV in the population aged above 20 years (Pal et al., 1972), while Madhavan et al. from Pondicherry showed that 84%~96% of adults had the antibody (Madhavan et al., 1974). All this data indicates previous exposures. However, primary infections are asymptomatic and rarely causes symptomatic disease in the immunocompetent individual (Cook and Zumlal, 2003). Symptoms associated with cytomegalovirus (CMV) infection in immunocompetent patients are also not well documented (Wreghitt et al., 2003). In immunocompetent patients, primary CMV infection typically runs an undifferentiated viral syndrome, or is manifested as heterophile antibody negative mononucleosis syndrome which is considered to be the most common clinical manifestation in immunocompetent hosts (Longo and Fauci, 2008). Most cases of CMV induced hepatitis occur in adults with severe immune deficiency and only a few cases involving immunocompetent patients have been reported. Majority of such cases are anicteric or mildly icteric, severe hepatitis is an uncommon presentation (Azad et al., 2008). Our patient was negative for HIV infection and there was no other evidence of immunosuppression. As described above he presented with severe jaundice with deranged liver function tests.  Again the central nervous system (CNS) is not spared in CMV infections observed in immunocompetent patients as shown by the study of Devetag and Boscariolo (2000). They proposed that two types of CMV meningoencephalitis can be observed in immunocompetent patients: the paroxysmal type, which is characterized by focal neurological symptoms or signs, alternating side of neurological deficits, headache, symptoms lasting from minutes to hours, and generally a benign outcome, and, also the monophasic type, which is characterized by more frequent occurrence of seizures, altered sensorium, symptoms lasting for days, and a less benign course. Our patient presented with the later type. Thus a clinical picture of acute hepatitis and acute meningoencephalitis in an immunocompetent individual was not expected to be a CMV infection especially in an Indian scenario. Though our patient had not given consent for liver and brain biopsy, but CMV DNA positivity and prompt clinical and virological response to antiviral treatment validated our diagnosis.

Patients displaying viremia early in the clinical course requires initiation of antiviral therapy to halt the progression to end organ disease (Griffiths, 2002). The use of antiviral treatment for CMV has proven to be of benefit in immunosuppressed individuals, but there is a scientific debate over the issues of treating CMV infection in cases of immunocompetent individuals (Manisha et al., 2011). Antiviral therapies such as ganciclovir, valganciclovir, foscarnet and cidofovir have been studied and are used in the treatment of CMV in immunocompromised host (Nazir and Eledrisi, 2015). Although several case reports have documented successful therapy of previously healthy patients with severe manifestations of CMV infection (Laing et al., 1997; Buonuomo et al., 2006), no clinical studies are available for the use of antiviral therapy in the immunocompetent host. We successfully treated our patient, with antiviral therapy as used for immunocompromised hosts with severe CMV infection.

Conclusion
The case of CMV infection we have reported, is rare in Indian perspective. Firstly CMV caused acute hepatitis and meningoencephalitis at the same time, simulating other common viral, bacterial and protozoal pathogens and could have delayed the diagnosis if not considered early. One should not ignore the possibility of CMV irrespective of immune status of the patient. Lastly though there are no conclusive facts regarding the beneficial effect of antiviral therapy in immunocompetent individuals, it may be initiated based on the clinical assessment along with positive CMV viral markers.

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