Chronic Graft Versus Host Disease in Liver

Chronic graft versus host disease affecting the liver is a serious complication that can develop months or even years after an allogeneic stem cell transplant, occurring when donor immune cells attack the recipient’s liver tissue.

Table of contents

• What Is Chronic Graft Versus Host Disease?
• How Chronic GVHD Affects the Liver
• Symptoms of Liver GVHD
• Diagnosing Liver GVHD
• Treatment Approaches
• Living with Chronic GVHD

What Is Chronic Graft Versus Host Disease?

Graft versus host disease (GVHD) is a condition that can happen after an allogeneic stem cell transplant, which is a procedure where a patient receives stem cells from a donor. In this transplant, the word “graft” refers to the donated stem cells, while “host” refers to the person who receives them^[1].

When GVHD occurs, the donor’s immune cells recognize the recipient’s body tissues as foreign and begin to attack them. This happens because the donor cells detect differences in proteins on the recipient’s cells^[2].

Chronic GVHD is different from acute GVHD, which typically develops within the first 100 days after transplant. Chronic GVHD usually appears more than three months after the transplant, though it can occur earlier or later. In most cases, symptoms appear sometime in the first year after transplant. Unlike acute GVHD, chronic GVHD starts very slowly and sometimes is hard to recognize^[5].

Chronic GVHD can affect many different organs and tissues in the body, including the skin, mouth, eyes, lungs, liver, gastrointestinal tract, muscles, and joints. The disease can follow acute GVHD, but it can also occur by itself in people who never had acute GVHD^[3].

• Liver
• Skin
• Gastrointestinal tract
• Eyes
• Mouth
• Lungs
• Joints

How Chronic GVHD Affects the Liver

The liver is one of the organs commonly affected by both acute and chronic GVHD^[1]. When chronic GVHD affects the liver, it can be challenging to diagnose because the symptoms and laboratory findings may be similar to other liver problems such as infection or drug-induced liver injury^[1].

In chronic GVHD, the liver involvement is largely an inflammatory process. This means the immune cells cause swelling and damage to liver tissue. Over time, this inflammation can lead to scarring and changes in how the liver functions^[6].

The diagnosis of hepatic (liver) GVHD requires careful attention to and correlation with clinical findings, laboratory values, and examination of liver tissue. This is because clinical signs and symptoms are frequently confounded by the overlapping effects of chemotherapy before transplant, medications used to prevent GVHD, and possible infections^[1].

Symptoms of Liver GVHD

The symptoms of chronic GVHD affecting the liver may not always be obvious at first. The most common signs that the liver may be involved include^[2][5]:

• Jaundice – a yellow discoloration of the skin and the whites of the eyes. This happens when a substance called bilirubin builds up in the body because the liver is not working properly.
• Dark-colored urine
• Light-colored or white stools

Some people with liver GVHD may not have any noticeable symptoms on the outside. The condition may only be detected through blood tests that show elevated liver enzyme levels. These are special proteins that leak into the bloodstream when liver cells are damaged^[5].

It’s important to remember that chronic GVHD can affect multiple organs at the same time. Many patients with liver involvement also have symptoms in other parts of their body, such as skin rashes, dry eyes and mouth, digestive problems, or breathing difficulties^[4].

Diagnosing Liver GVHD

Diagnosing chronic GVHD in the liver requires a comprehensive approach. Healthcare providers must consider many factors because the symptoms can look similar to other liver problems^[1].

The diagnosis typically involves several steps. Blood tests are used to check liver function by measuring specific enzymes and bilirubin levels. These tests help doctors understand how well the liver is working and whether there are signs of damage^[5].

In some cases, a liver biopsy may be needed. This is a procedure where a small sample of liver tissue is removed and examined under a microscope. The biopsy helps doctors see the specific changes in the liver tissue and distinguish GVHD from other conditions. However, before performing a biopsy, the transplant team will consider all other possible causes for the symptoms^[5].

Healthcare providers must carefully review the patient’s medical history, including what medications they are taking, whether they have had any infections, and whether they had acute GVHD earlier. All of this information helps determine whether the liver problems are due to chronic GVHD or something else^[1].

Treatment Approaches

Treatment of chronic GVHD affecting the liver varies based on the severity of symptoms and how well the patient responds to therapy. Most patients are treated with medications that suppress the immune system, which helps reduce the attack on the liver and other affected organs^[5].

The most commonly used medications include corticosteroids (such as prednisone or methylprednisolone), which are powerful drugs that reduce inflammation. Other medications frequently used are calcineurin inhibitors like cyclosporine or tacrolimus. These drugs work by weakening the donor cells’ ability to attack the patient’s body^[5][8].

Treatment typically requires immunosuppressive medications for a median of one to three years. The duration and intensity of treatment must be carefully calibrated over time to avoid overtreatment or undertreatment. This requires close monitoring and regular follow-up with the transplant team^[6].

Before trying oral or intravenous medications that affect the whole body, physicians may try some local therapy to decrease the side effects from the medications. The goal is to find the right balance between controlling the GVHD and minimizing side effects from the treatments^[5].

Because immunosuppressive drugs weaken the immune system, patients receiving treatment for chronic GVHD are at higher risk for infections. For this reason, patients are usually given prophylactic (preventive) medications to protect against viral, fungal, and bacterial infections^[5].

Living with Chronic GVHD

Living with chronic GVHD affecting the liver can be challenging. The disease and its treatment can have significant effects on daily life, physical functioning, and emotional well-being. Many people who have chronic GVHD describe managing it as a “full-time job”^[10].

Chronic GVHD is associated with increased overall morbidity and mortality. It remains a major cause of late death after transplant, despite improvements in transplant procedures and supportive care. The functional consequences of chronic GVHD are major determinants of the health and quality of life of transplant survivors^[6][15].

Because chronic GVHD and its treatment cause profound immunosuppression, the main problem is the patient’s inability to fight infections. This means patients must take extra precautions to avoid exposure to germs and must take preventive medications regularly^[5].

Managing chronic GVHD often requires working with multiple healthcare providers. Keys to successful management include early recognition and diagnosis, comprehensive evaluation at the onset and periodically during the course of the disease, prompt institution of treatment, appropriate monitoring of response, and the use of supportive care to prevent complications and disability^[6].

Many transplant centers work in partnership with community physicians to provide shared care for patients with chronic GVHD. This collaborative approach enables referring physicians to manage long-term administration of immunosuppressive medications and supportive care with guidance from transplant center experts. Effective communication between all members of the healthcare team is essential for optimal patient care^[6][13].

Emotional and psychological support is also important for people living with chronic GVHD. The condition can bring challenges with physical functioning, fatigue, general health, social functioning, and psychological distress including depression and anxiety. Patients should tell their healthcare provider if they are struggling, as they may be able to provide referrals to supportive care services^[10][11].