The Lupus Adventurer is extremely pleased to introduce guest-blogger, Donald E. Thomas, Jr., MD, FACP, FACR, author of The Lupus Encyclopedia. After Johns Hopkins University Press releases his book in May 2014, you can expect a book review here.
Dr. Thomas is an assistant professor of medicine at the Uniformed Services University of the Health Sciences and teaches rheumatology at the Walter Reed National Military Medical Center. He is a practicing physician and currently serves as a member of the Medical-Scientific Advisory Council of the Lupus Foundation of America, DC/MD/VA chapter, and brings the authoritative medical knowledge to this discussion of lupus and its potential effects on the liver.
While only a small percentage of systemic lupus patients will develop liver involvement, this subject is of special interest to the Lupus Adventurer. When lupus liver problems started, it was a major treatment turning point. Liver problems began after ten years of taking methotrexate and Imuran (azathioprine,) and it took another year and three doctors to confirm it. After stopping these drugs, eventually infusions of an investigational biologic drug, Rituxan (rituximab) during participation Phase III clinical trials controlled the lupus hepatitis.
Now, after receiving Benlysta (belimumab) for the past couple of years, both liver and lupus remain under excellent control. Past posts have discussed lupus liver-involvement from a patient’s perspective, and now, Dr. Thomas shares his outstanding article with us about Lupus Hepatitis from a physician’s view.
By Donald Thomas, M.D.
Three Major Causes of Hepatitis
Hepatitis simply means “inflammation of the liver.” Many of us immediately think of a contagious hepatitis when we hear the word hepatitis, but the reality is that there are numerous causes of hepatitis. Viral infections (especially hepatitis A, hepatitis B, and hepatitis C) can be contracted from other people and cause hepatitis, yet medications (especially medicines related to aspirin) are the most common cause of hepatitis in people who have systemic lupus erythematosus (SLE). Since Lupus can “attack” virtually every part of the body, SLE can directly cause inflammation of the liver itself. That will be the primary subject of this article.
The liver is a very large organ that lies in the upper right side of your abdomen. Most of it is located beneath the lower ribs on the right side of your body. It has many different jobs to do in order to keep us healthy. These vital jobs include filtering waste products from the blood, removing bile, storing energy for the body, producing important proteins, and even producing important hormones.
With mild inflammation, most people do not feel ill at all. Mild inflammation of the liver (hepatitis) may simply cause abnormalities with some of the liver blood tests, especially ALT, bilirubin, and alkaline phosphatase levels. Some or all of these blood tests can become elevated due to hepatitis. However, these blood tests may become elevated for reasons other than hepatitis.
For example, ALT can become elevated due to inflammation of the muscles; bilirubin can become elevated in some types of anemia, and alkaline phosphatase can become elevated due to bone problems. However, elevations in these test results are usually the first clue that there may be something going on with the liver. It is up to the doctor to figure out what is causing the elevation, and this usually involves additional testing.
If hepatitis is severe, then the function of the liver can become compromised, leading to problems such as fatigue, loss of appetite, and even jaundice. (In jaundice, symptoms include the whites of the eyes and skin turning yellow due to too much bilirubin in the blood stream). If hepatitis becomes severe and a lot of the liver becomes irreversibly damaged, scar tissue can replace the damaged liver tissue. We call this condition “cirrhosis”. People who develop cirrhosis may end up needing a liver transplant if it becomes severe enough.
Liver Blood Tests
All patients who have SLE realize very early in their illness that they need frequent blood and urine tests to monitor how their lupus is doing, and to monitor their medications. It is important to ensure that no side effects are occurring from the medicines. Mild elevations of the liver enzymes, such as ALT, are very common in people who have SLE. The most common cause is from the medications that we use. Generally, small rises in ALT level from medications is perfectly fine, and usually doesn’t cause liver problems except for slightly abnormal blood tests. However, if they become too high, then sometimes the offending medication must be stopped or the dose lowered.
However, when we (doctors) note elevations of liver enzymes more than once or twice, we usually do additional tests. We need to make sure it isn’t something other than a mild medication effect. We will usually ask the person not to drink any alcohol (which can raise the liver enzymes), and request lab work for other potential causes, such as viral hepatitis B and hepatitis C. We usually order additional tests to make sure other causes of hepatitis are not present such as genetic causes (e.g. hemochromatosis). Sometimes, we may do imaging studies such as an ultrasound or CT scan of the liver to see if there is any “fatty liver” or “gall bladder stones,” or other potential causes that imaging might reveal.
Although rare with SLE, autoimmune hepatitis is one consideration. This is a disease where the immune system attacks the liver and causes inflammation. Without proper treatment, it has a high rate of progression to cirrhosis. We usually order antibodies such as mitochondrial, actin, liver/kidney microsome, and smooth muscle antibodies to look for this possibility. It is treated with some of the same medications we use to treat lupus such as steroids and azathioprine (Imuran).
Approximately 1 out of 20 people (5%) who have SLE will develop inflammation of the liver directly due to their lupus. We call this “lupus hepatitis.” It usually shows up with elevations of the liver blood tests mentioned above. After we “rule out” other causes (as discussed above), the only way to know if someone has “lupus hepatitis” is to get a liver biopsy. It is important to realize that “autoimmune hepatitis” discussed in the previous paragraph is a different problem than “lupus hepatitis.” Although both are due to the immune system causing inflammation of the liver, “autoimmune hepatitis” more commonly can be severe and progress to cirrhosis. “Lupus hepatitis” typically responds to treatment more easily.
A biopsy is a medical procedure where the doctor removes a small piece of tissue from the body to study it under a microscope and see what is going on. A liver biopsy is generally a very safe outpatient procedure. The doctor numbs the skin and soft tissues covering the liver, and then inserts a biopsy needle through the numb area to remove small pieces of liver for analysis. Most people are free to go home within a couple of hours after the procedure is finished. 3-7 days later, the results of the biopsy are usually ready.
The biopsy results seen in “lupus hepatitis” are very nonspecific. often showing liver inflammation that is seen in many different causes besides lupus. The primary reasons for the biopsy are to ensure that other causes of hepatitis are not present (such as hemochromatosis), to assess how much inflammation is occurring, and to ensure that there is no scar tissue from cirrhosis.
Lupus Hepatitis is Usually Controllable
Fortunately, “lupus hepatitis” tends to be a mild condition. In today’s medical environment almost everyone with SLE is treated immediately (hopefully) with medications such as Plaquenil (hydroxychloroquine), so lupus hepatitis is not very common. When it does occur, it tends to be mild in severity. Prior to today’s treatments, or in cases where SLE is severe and not identified early enough, severe hepatitis may occur.
Hepatitis can potentially cause an enlarged liver (hepatomegaly), jaundice (yellow skin and eyes), and even cirrhosis. Severe cases may need strong immunosuppressant medications such as prednisone and azathioprine (Imuran). A study released in 2011 in the journal Lupus demonstrated that 14 SLE patients who were followed over 10 years did not progress to cirrhosis. This study confirms the opinion of many lupus experts, that lupus hepatitis is easily controlled in most of our patients.
Inflammation of the liver due to SLE (lupus hepatitis) is uncommon, only occurring in 5% of patients. With proper treatment, it tends to be mild, and rarely progresses to permanent liver damage (cirrhosis). It is initially picked up by doctors by observing elevated liver blood tests (e.g. ALT, bilirubin, and alkaline phosphatase levels), followed by other blood tests, imaging studies, and sometimes a liver biopsy in order to diagnose it.
Piga M, Vacca A, Porru G, P Garau P, Caulia A, Mathieu A. Two different clinical subsets of lupus hepatitis exist: mimicking primary autoimmune liver diseases or part of their spectrum? Lupus. 2011;20:1450–1451.