What Is Cytomegalovirus Hepatitis?

Overview

Cytomegalovirus hepatitis is inflammation of the liver caused by cytomegalovirus. It is extremely rare in people with healthy immune systems.

Cytomegalovirus (CMV), also known as human herpesvirus 5, is a member of the herpes virus family.¹ The virus is extremely common, and found in 60-100% of people worldwide. Most healthy people with the infectious disease have no symptoms or minor cold/flu-like symptoms. However, in those with a weakened immune system (immunocompromised), CMV can infect the liver and cause hepatitis which can lead to chronic disease.

Causes of cytomegalovirus hepatitis

Cytomegalovirus hepatitis is caused by infection with human cytomegalovirus which is transmitted through bodily fluids such as saliva, urine, tears, blood, breast milk, and genital secretions.¹ It can be spread through close contact with infected people, often through young children at nursery, but can also be passed through organ transplantation, blood transfusion, breast milk and from pregnant women to the foetus.^2,3 

When CMV is active in the body it can infect lots of different cells.⁴ The enlargement of these infected cells is where the name of the virus comes from (‘cyto’ meaning cell and ‘megal’ meaning big).¹ The virus has an incubation period in the body of 4-6 weeks during which it can multiply and spread in the body and to other people; after this, the virus becomes latent where it is present in cells but is in a resting state and not producing more virus. People who are immunocompromised are particularly vulnerable to CMV reactivation from the latent state.² 

Most healthy people’s immune systems can fight the virus effectively. However, in immunocompromised people, both the primary CMV infection and reactivation can infect and cause damage to the liver, leading to hepatitis. 

Examples of other organs that can be infected by CMV are the large intestine (CMV colitis)⁵, the retina, which is in the eye, (CMV retinitis)⁶ and the lungs (CMV pneumonia).⁷ 

Signs and symptoms of cytomegalovirus hepatitis

The signs and symptoms of a cytomegalovirus infection depend on age and immune status.¹ Immunocompetent patients are usually asymptomatic; rarely they may experience cold/flu-like symptoms such as a sore throat. In some cases, infected people may develop CMV mononucleosis.⁴ 

Immunocompromised people are vulnerable to more severe CMV disease which often presents as fever, chills or rigours. Infection of individual organs will have different presentations depending on the organ. Common signs of hepatitis include:⁸

• Upper right abdominal pain
• Elevated liver enzymes
• Liver inflammation/enlargement
• Jaundice

If untreated, hepatitis can lead to liver failure and even death.

Risk factors

The biggest risk factor for CMV hepatitis is being immunocompromised.⁹ This includes:

• Those that have an HIV infection or AIDs
• Those that have received an organ transplant, particularly a liver transplant
• Those that are using immunosuppressing medications such as steroids
• Babies infected in utero (congenital CMV infection) and low birth rate/premature infants

In healthy patients, clinically significant CMV hepatitis is very rare but it is possible.⁴

If someone who is immunocompetent does develop hepatitis then usually it will quickly be fought off by the immune response. In people who have a weakened immune system, hepatitis can persist for longer and have a more detrimental effect on the liver. 

Management and treatment for cytomegalovirus hepatitis

Rarely does a cytomegalovirus infection require treatment, even if acute hepatitis develops. However, severe cytomegalovirus infections are usually treated with antivirals such as ganciclovir and valganciclovir to suppress the virus.⁸ The length of treatment is determined by monitoring how much of the virus is in the patient's blood.¹⁰ In all instances, if the patient is experiencing abdominal pain they can be treated with pain medication.

Organ transplant patients, particularly liver transplant recipients, are at high risk of CMV infection so they often receive one of two types of preventive treatment:⁴ 

• Prophylaxis therapy where antivirals are started after transplantation and taken for at least 3 months 
• Preemptive therapy where the recipient is closely monitored for the presence of CMV and, if identified, antiviral treatment is started

Diagnosis of cytomegalovirus hepatitis

A true diagnosis of CMV hepatitis requires a liver tissue biopsy but a combination of blood tests can provide faster results and can also be used to monitor disease progression and treatment response.⁴ For doctors to diagnose CMV hepatitis the tests must indicate infection with CMV as well as inflammation of the liver.

Examples of tests that might be run include:

• Liver tissue biopsy - A small piece of liver tissue is taken, usually by inserting a thin needle into the neck or stomach. The sample is stained and looked at under a microscope to confirm the presence of the CMV virus
• Elevated bilirubin and/or liver enzymes -  Bilirubin is a fluid found in the liver. Enzymes found in the liver include alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT). If elevated levels of any/a combination of these are found in the blood it could indicate problems with the liver
• Serology - Serology is when blood is checked for the presence of antibodies, in this case, CMV IgM and CMV IgG (CMV seropositivity). If the body has made antibodies against an active CMV infection then these will be detected in the blood. However, this test is not useful in immunocompromised people who have an impaired immune response and may not make enough antibodies to be detected
• Antigenemia - Antigenemia is a method of detecting CMV antigens in the blood
• Viral culture - A sample of body fluid or tissue is put into cells to see if the virus grows. Sometimes this test is not useful because it takes a long time
• Polymerase chain reaction (PCR) - CMV PCR is used to detect CMV DNA in the blood. PCR is very quick and sensitive so it is often a preferred technique

Complications

Complications of CMV hepatitis include sepsis and liver failure.¹¹ In rare cases, liver failure can require a liver transplant. 

In post-liver transplant patients, CMV infection has been associated with chronic rejection.⁴

FAQs

How can I prevent cytomegalovirus hepatitis?

For most healthy people cytomegalovirus does not pose any risk and the majority of people will be infected at some point. For immunocompromised people, the risks are much greater and those infected with CMV can become very ill because their immune response is poor. Immunocompromised people should practice good hand hygiene, safe sex and avoid people who are sick. 

Antivirals can be used as a preventative in organ transplant recipients.

How common is cytomegalovirus hepatitis?

Even though cytomegalovirus is very common it rarely causes complications in healthy people. Cytomegalovirus hepatitis in immunocompetent patients is very rare. 

In immunocompromised people, particularly liver transplant recipients, the risk of CMV hepatitis is much greater. 

When should I see a doctor?

If you are usually healthy, you should see a doctor if you experience a persistent fever or abdominal pain over a few weeks that doesn’t improve. If you have obvious signs of liver problems such as jaundice or specific pain in the upper right abdomen then visit your doctor straight away. Immunocompromised people are more vulnerable so they should seek medical attention as soon as they exhibit any signs of infection. 

Summary

Cytomegalovirus (CMV) is a member of the herpes virus family. It is very common and most healthy people won’t even know they have been infected. Immunocompromised people are much more vulnerable because of their weakened immune systems; infection with CMV can be severe and lead to organ damage. If CMV infects the liver and causes inflammation this is known as CMV hepatitis. CMV hepatitis is most common in liver transplant recipients and can cause chronic rejection so these patients often receive preemptive treatment after transplant. In other cases, CMV hepatitis is usually only treated with antivirals when it is severe. CMV hepatitis can be hard to diagnose because signs of hepatitis are not always obvious without testing. Doctors may take a liver tissue biopsy or use a combination of blood tests to make a diagnosis. In rare cases, CMV hepatitis can lead to complications such as sepsis and liver damage. If you suspect you may have CMV hepatitis, particularly if you are immunocompromised, then you should seek medical advice.