The Connection Between Mono and Hepatitis

When people hear the word "hepatitis," they generally take that to mean viral hepatitis such as hepatitis A, hepatitis B, or hepatitis C. And while these are certainly the most common forms of hepatitis (liver inflammation), there are other infectious causes—among them, infectious mononucleosis caused by the Epstein-Barr virus (EBV).

Unlike some forms of hepatitis, hepatitis caused by mononucleosis (also known as glandular fever, "mono," or the "kissing disease") is almost always self-limiting with generally milder symptoms. Treatment is mainly supportive.

Hepatitis in people with mononucleosis is often referred to as Epstein-Barr virus hepatitis, or simply EBV hepatitis.

Symptoms

Hepatitis is the inflammation of the liver. It has many causes, both infectious (viral, bacterial, parasitic) and non-infectious (including alcoholism, nonalcoholic fatty liver disease, and certain autoimmune disorders).

Hepatitis can also be acute (inflammation begins suddenly and lasts for only a few weeks) or chronic (lasts more than six months and sometimes is permanent). Some acute infections can become chronic after the initial symptoms resolve, such as that seen in some people with hepatitis B and C.

Hepatitis is an uncommon presentation of mononucleosis but can occur when the EBV infection is especially severe. The acute hepatitis symptoms will typically appear and resolve within the course of the EBV infection (usually two to four weeks) and tend to be milder than other forms of infectious hepatitis.

Symptoms commonly seen with EBV hepatitis include:

• Extreme fatigue
• Upper abdominal swelling or pain just beneath the right ribs
• Nausea or vomiting
• Clay-colored stool
• Dark urine
• Loss of appetite
• Low-grade fever
• Joint aches

Once the acute symptoms resolve, the liver function will typically return to normal with no long-term injury to the liver itself.

With that said, EBV hepatitis can become severe and even life-threatening in some people, particularly immunocompromised people in whom the condition can lead to acute liver failure. This is an extremely rare complication, affecting less than 0.25% of people with mononucleosis, but is associated with a high mortality rate.

Causes

Mononucleosis is a viral infection typically associated with EBV (although around 5% of cases are linked to another virus known as cytomegalovirus). EBV is easily spread from person to person via saliva. As a result, around 95% of the world's population will have been exposed to EBV by the age of 40.

EBV infection can often be asymptomatic (without symptoms) or subclinical (without notable symptoms), particularly in young children. Even so, the infection will almost invariably cause the elevation of liver enzymes known as transaminases.

Increases in transaminases often occur when there is a problem with the liver, during which the enzymes meant to break down toxins start to leach into the bloodstream. In most cases of mononucleosis, the elevation will be mild and transient, causing little if any liver-related symptoms.

However, on rare occasions when transaminase levels are five to 10 times higher than normal, EBV hepatitis can become symptomatic. EBV hepatitis typically occurs alongside characteristic symptoms of mononucleosis, although it has been known to occur in isolation in some people.

The risk of EBV hepatitis is also thought to be greater in people with underlying hepatitis B or C infection; EBV may, in fact, be one of the factors linked to chronic hepatitis infection. EBV may also indirectly cause hepatitis by acting as a trigger to autoimmune hepatitis (AIH).

Symptoms of mononucleosis can overlap those of EBV hepatitis and may include:

• Headache
• Persistent fatigue
• Mild fever, usually lasting for around two weeks
• Sore throat, lasting for anywhere from three to 10 days
• Tonsillitis, sometimes with pus
• Swollen lymph nodes, mainly around the back of the neck (known as the cervical lymphadenopathy)
• Enlarged spleen (splenomegaly)

EBV hepatitis is especially concerning in people who have undergone a liver transplant. The infection may cause organ rejection or increase the risk of post-transplant lymphoproliferative disorders (PTLDs).

Diagnosis

When symptoms of hepatitis develop, the doctor will typically perform a series of antibody tests known as a viral hepatitis panel that can detect the three most common causes of hepatitis, namely hepatitis A, B, and C.

With that said, infectious mononucleosis should be suspected in teens or young adults who also present with a sore throat, enlarged tonsils, or cervical lymphadenopathy. In fact, EBV should be explored in anyone with unexplained hepatitis symptoms, irrespective of age.

Healthcare professionals typically diagnose infectious mononucleosis based on symptoms. But blood tests and other procedures may be ordered if there are signs of hepatitis, in part to confirm that EBV is the cause and in part to rule out other potential causes.

Blood tests may include:

• Viral capsid antigen (VCA) test: Used to confirm acute mononucleosis by detecting EBV antibodies that typically disappear within four to six weeks of infection
• EBV nuclear antigen (EBNA) test: Used to detect EBV antigens two to four months after infection or even longer, as they persist for life
• Liver functions tests (LFTs): Used to detect elevations of transaminase enzymes known as aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
• White blood cell (WBC) count: Used to detect abnormal elevations in the lymphocyte count (a characteristic sign of EBV hepatitis)

If the findings are ambiguous or the symptoms are severe or unusual, the doctor may order a liver biopsy in which a sample of liver tissue is obtained using a needle through the abdominal wall.

When examined under the microscope, the tissues will often show thick clusters of lymphocytes, typically in a single-file "string-of-pearl" pattern. That—and the lack of liver scarring (fibrosis)—can help differentiate EBV hepatitis from other forms of hepatitis.

To definitively diagnose EBV hepatitis, the doctor will exclude other possible explanations in their differential diagnosis, including:

• Alcoholic hepatitis
• Autoimmune hepatitis
• Cytomegalovirus (CMV) hepatitis
• Drug-induced liver injury
• Lymphomas
• Nonalcoholic fatty liver disease (NAFLD)

Treatment

The treatment of EBV hepatitis is generally supportive since most cases will resolve on their own after the infection runs its course. This typically involves rest, avoidance of contact sports, plenty of hydration, balanced nutrition, and over-the-counter nonsteroidal anti-inflammatory drugs (NSAIDs) like Advil (ibuprofen) to relieve fever and body aches.

Tylenol (acetaminophen) is typically avoided due to the adverse impact it can have on the liver. The avoidance of alcohol is also key.

Despite their uncertain benefits, antivirals used to treat mononucleosis cause few side effects (mainly stomach ache, nausea, diarrhea, and headache). However, they can lead to antiviral resistance if overused or not used appropriately.

Liver transplant recipients who develop acute EBV may require a change of treatment to help reduce viral activity and the risk of organ rejection. To this end, many doctors will temporarily stop immunosuppressants like Azasan (azathioprine) that leaves the body vulnerable to infection and increase corticosteroids like prednisolone that help reduce liver inflammation.

A Word From Verywell

Prevention is key to avoiding EBV hepatitis, particularly if you are immunocompromised or have recently undergone a liver transplant.

Because EBV is primarily transmitted through saliva, you would need to avoid sharing straws, food, utensils, cigarettes, inhalers, lipstick, or lip balm. Washing your hands and avoiding close contact with anyone who is sick (including kissing) is also essential.

As ubiquitous as EBV is, don't assume that you have it and can ignore the simple guidelines. Taking a few reasonable precautions may not only spare you the rigors of symptomatic mono but can also protect you from other saliva-borne infections such as herpes simplex virus (HSV).