Fate of Acute Cytomegalovirus Hepatitis in an Immune Competent Host
Mohamed Lotfy Asser
Department of Internal Medicine, Medical Research Institute, University of Alexandria, Egypt
*Corresponding author: Mohamed Lotfy Asser, Department of Internal Medicine, Medical Research Institute, University of Alexandria, Egypt, Tel: +201224394475; E-mail: firstname.lastname@example.org
Citation: Asser ML (2019) Fate of Acute Cytomegalovirus Hepatitis in an Immune Competent Host J Clin Gastroenterol Dig Disord 2019: 7-10.
Received: 27 October, 2018; Accepted: 22 March, 2019; Published: 27 March, 2019
Acute Cytomegalovirus (CMV) infections are widely distributed worldwide, with seroprevalance of 30-100% of general population, and a high rate of subclinical infections. Most of the cases pass silently, or complain of a group of non-specific symptoms that are usually mild and self-limited especially in immune competent individuals. Complications from acute CMV infections may rarely occur particularly in immune compromised individuals, affecting many organs including the liver, causing elevated liver Transaminases, jaundice and may even lead to acute liver failure requiring the use of antiviral therapy. In this case report, we describe a rare case of acute CMV hepatitis in a 34 years old immune competent male, who presented with fever, fatigue, elevated Transaminases and jaundice, which resolved completely without the need for antiviral therapy.
Keywords: Cytomegalovirus; Infections; Seroprevalance; Immune competent
Cytomegalovirus (CMV) infection has a worldwide impact because of its high congenital infection rates, disease burden and associated costs. CMV is a double-stranded DNA virus that belongs to the family Herpesviridae and the subfamily Beta-herpesviridae. It is called Human Herpes Virus type 5. It has a seroprevalence of 30 to 100% depending on age, geographical distribution, ethnic race as well as social and immune status of the individual. Transmission occurs through secretions like tears, saliva, urine, genital secretions, breast milk and blood. The incubation period is 4–6 weeks [1-3].
The virus may remain clinically asymptomatic or manifest by a group of non-specific flu like symptoms as fever (should be included in differential diagnosis of fever of unknown origin), fatigue, cough, sore throat, lymph nodal and splenic enlargement (should be included in differential diagnosis of lymphadenopathy) in immune competent individuals, afterwards, it remains latent throughout life and may reactivate later on [1,4].
On the other hand, infection in immune compromised individuals usually manifest as a mononucleosis syndrome. It can affect any organ of the body resulting in fever, pneumonia, hepatitis, encephalitis, myelitis, colitis, uveitis, retinitis and neuropathy. Rarely it may cause Guillian-Barre syndrome, meningoencephelitis, pericarditis, myocarditis, thrombocytopenia and hemolytic anemia [1,5].
In HIV patients, CMV infection may involve the whole gastro-intestinal tract. Retinitis is the most common manifestation in HIV patients.
A 34 years old apparently healthy male from Alexandria, Egypt living in urban, working in the field of poultry with occasional direct exposure to chicken and their products, non-smoker, presented to our outpatient clinic with fever and fatigue for 1 week. The fever was described as being high grade (exceeded 39 degrees measured orally by a mercury thermometer), persistent, decreased only by intra-muscular injections of non-steroidal anti-inflammatory drugs temporarily then increased again, associated with malaise, chills, loss of appetite and dry cough. The patient denied recent travelling abroad, contact with a tuberculosis patient or taking any drugs or narcotics. He had a negative medical and surgical history, no history of allergies and no history of a similar illness.
Physical examination of the patient including throat, chest, abdominal and lymph nodal examination were unremarkable and revealed no abnormalities. The patient was prescribed Paracetamol and cold compresses when fever increased above 38.5 degrees and plenty of oral fluids were advised.
Several investigations were ordered including chest X-ray, abdominal ultrasound, urine, stool and blood tests. The investigations showed leukocytosis 12 K/cmm with 69% lymphocytosis, serum Bilirubin total portion of 2 mg/dl and direct portion of 1.4 mg/dl, ALT 223 U/l, AST 180 U/l, ALP 149 IU, serum albumin 3.6 gm/dL, Prothrombin activity 80%, INR 1.2, LDH 480 U/l, CRP 72.8 mg/L and ESR 1st hour 15 mm/h. Otherwise, all other investigations were negative including urine and stool analysis, serum Lipase, Calcium, Phosphorous, HAV-Ab, HCV-Ab, HBs Ag, Widal test for Salmonella Typhi and Paratyphi and Brucella, abdominal ultrasound and chest X-ray. Here a primary diagnosis of acute hepatitis was settled for further work-up to find out the cause.
Silymarin was prescribed to the patient and bed rest was advised ensuring good hygienic care, and further work-up was done. These investigations showed a positive CMV-IgM test and otherwise negative blood tests. The debate here was whether to either give antiviral therapy to that patient or just wait and see offering only conservative and supportive measures.
Hepatic Transaminases, serum Bilirubin level and complete blood count were repeated every three days, blood tests started to improve on the third week of illness until reaching normal levels, as well as the seroconversion of CMV IgM, during which fever started to become low grade, intermittent and more controlled with improvement of the general condition of the patient.
The patient here was diagnosed as a rare case of acute hepatitis complicating acute CMV infection, in an apparently healthy immune competent individual. The case was followed up cautiously, clinically and by doing investigations without giving any antiviral therapy. The condition improved and completely resolved with normalization of liver Transaminases and serum Bilirubin.
CMV is the most common cause of congenital infections worldwide. It is also known to be a major cause of mortality in immune compromised patients. The prevailing age of infection varies worldwide. In developing countries, most infections are acquired during childhood, while in developed countries; up to 50% of young adults are seronegative. The gold standard to confirm the diagnosis is the presence of CMV-antibodies IgM and/or a rising IgG titre in blood using an immune assay or a Polymerase chain reaction, which can be either qualitative or quantitative that measures the amount of viral DNA [1,4,5].
CMV disease typically presents as a mild and self-limited Mononucleosis like syndrome without an organ complication. Therefore, in immune competent individuals no treatment is required [1,3]. On the other hand, CMV infection is more often complicated in HIV patients and immune compromised patients as those with a transplanted organ or on immune suppressive therapy. Complications may occur as retinitis, esophagitis, or enteritis. Other complications include peripheral neuropathy, pneumonitis, gastritis, colitis, or hepatitis may also occur [1,5].
Hepatitis is a rare but a reported complication of acute CMV infection that usually requires no antiviral therapy due to its self-limited course. Antiviral therapy is reserved for severe CMV infections because of its potential side effects that include myelosuppression, central nervous system disorders, irreversible infertility (inhibition of spermatogenesis) and teratogenesis [1,6].
Differential diagnosis of acute hepatitis includes a wide range of diseases and infections. This could be categorized into viral infections as Hepatitis A, B, C, D and E, CMV, EBV, HSV, VZV and yellow fever, bacterial infections as Typhoid fever, Q fever, leptospirosis, secondary syphilis and sepsis, parasitic infections as toxocariasis and liver flukes, drug induced as aspirin, acetaminophen, rifampin, oral contraceptives and sulfonamides, toxins as alcohol and carbon tetrachloride and autoimmune diseases as autoimmune hepatitis and SLE. All these diseases and conditions may vary clinically from flu like symptoms to acute liver failure and hepatic encephalopathy .
Acute CMV infection could be detected by culture of fibroblasts, serology, antigen assays, PCR and cytopathology. In transplant population, antigen assays or PCR is used for diagnosis and treatment determinations. Elevated serum IgM level or a 4-fold increase in IgG titers is sufficient for diagnosis of recent CMV infection .
Indications for antiviral therapy are mostly based on the clinical course as well as the individual immune status. Several agents are currently available for the treatment of CMV infection and disease. When antiviral therapy is needed, it should be given for at least 2 to 3 weeks. The end point of therapy is the documented clearance of virus from the blood. To avoid a relapse after intravenous therapy, oral treatment with Valganciclovir for 2 to 3 months may be given for high-risk patients [1,9,10].
Other antiviral treatment options include Ganciclovir, Cidofovir, Foscarnet and Letermovir, which is used for CMV prophylaxis in adult CMV-seropositive recipients of allogenic hematopoietic stem cell transplantation. CMV immune globulins (CMV Ig) derived from healthy blood donors with high CMV titers provide a passive source of antibodies against CMV, especially used for CMV pneumonia. Also, Leflunamide has been used in the treatment of CMV disease in transplant recepients, as well as in prevention of acute and chronic rejection in recipients of solid organ transplants .
Acute Cytomegalovirus hepatitis is an important differential diagnosis in immune competent adults presenting with non-specific flu like symptoms and hepatitis of unknown cause.
Antiviral therapy with intravenous Valganciclovir and Ganciclovir is reserved for severe and life-threatening cases of acute Cytomegalovirus infections. Treatment should be individualized, weighing the risks of medication adverse effects versus the benefits of improving disease outcome as most of patients respond to conservative measures.