What is Granulomatous Hepatitis?
Granulomatous hepatitis is a term used when there are clumps of immune cells – “granulomas” – in the liver. This condition can have various causes; in the US, it’s usually due to sarcoidosis or primary biliary cholangitis, while globally, tuberculosis is a common cause. Due to the increasing use of imaging technologies like CT scans and MRI, granulomas in the liver may also be discovered by accident. Most of the time, they indicate some kind of systemic issue in the body.
The symptoms may include abdominal pain in the right upper part of the tummy, a rise in certain liver-specific enzymes (like alkaline phosphatase and transaminases), high levels of bilirubin in the blood (which can cause jaundice), or even fevers. In terms of treatment, it’s important to identify and target the root cause of the problem.
What Causes Granulomatous Hepatitis?
Hepatic granulomas, or lumps in the liver, can occur due to a number of infectious or non-infectious causes. The most common causes include sarcoidosis (a disease that causes inflammation and tiny lumps in organs), primary biliary cholangitis (a disease that damages the liver’s bile ducts), tuberculosis, and drug-induced liver injury.
In the US, the top causes are sarcoidosis and primary biliary cholangitis, while tuberculosis is most common worldwide. Many types of drugs have been linked with hepatic granulomas, including some diabetes drugs, seizure medicines, antibiotics, and drugs for blood pressure and heart rhythm. Exposure to toxic substances like beryllium and silica has also been linked to the condition, likely due to allergic reactions.
Talc, barium, and silicone from certain medical procedures can also cause hepatic granulomas. Other sources of this condition can include chronic infections from hepatitis B and C, Bacille Calmette-Guerin (BCG) therapy, several types of infectious diseases, abscesses from parasites, lymphoma, and unknown types of granulomas. There’s also a type of hepatic granulomas called “idiopathic granulomatous hepatitis,” which is usually associated with long-lasting fevers, muscle pain, joint pain, and enlargement of the liver and spleen, and it has an unknown cause.
Risk Factors and Frequency for Granulomatous Hepatitis
Hepatic granulomas, or small clumps of immune cells often found in liver tissue, are quite common. This is because the liver is full of cells that help the body fight off diseases. These granulomas appear in 2% to 10% of liver biopsies. However, these formations can be either a natural reaction to harmful stimuli or a sign of certain diseases, which makes diagnosis a challenge. In fact, after thorough examinations, about 10% to 36% of hepatic granulomas cannot be linked to a specific cause.
One relevant condition linked to hepatic granulomas is systemic sarcoidosis, which may involve the liver and spleen in 50% to 70% of cases. The condition called primary biliary cirrhosis (PBC) can also cause granulomas in about 25% to 50% of patients.
Forms of tuberculosis can cause hepatic granulomas too, with pulmonary tuberculosis resulting in hepatic granulomas in 25% of cases, and the more severe miliary tuberculosis in up to 90% of cases. In fact, tuberculosis and sarcoidosis are the most common causes, accounting for about 50% to 65% of cases of granulomatous hepatitis, or inflamed liver.
Also, a kind of hepatitis caused by Histoplasmosis is also typically found in the midwestern and central parts of the United States, especially the Ohio River Valley. It accounts for about 12% of cases in Ohio. In addition, Coccidioidomycosis, a fungal disease, is commonly found in the southwestern parts of the US.
Signs and Symptoms of Granulomatous Hepatitis
Hepatic granulomas, a form of liver disease, usually don’t have symptoms on their own, nor do they always show up in lab tests. The symptoms people experience usually come from other health problems the person has. To diagnose hepatic granulomas, doctors will do a full medical history and a physical examination. If a patient is experiencing general symptoms of illness such as lasting fevers, night sweats, chills, weight loss, loss of appetite, muscle aches, and joint aches, their doctor might think about hepatic granulomas as a possibility, especially if the patient also has belly pain and tenderness, specifically in the upper right side, unexplained fever, an enlarged liver, or mild abnormal liver tests.
Patients with this condition may also have fluid buildup in the abdomen, visible blood vessels on the skin, liver scarring with high blood pressure in the abdomen and liver cirrhosis. This can be seen in certain conditions like primary biliary cholangitis, sarcoidosis, or schistosomiasis. When diagnosing, doctors will also consider important lifestyle factors. These can include the patient’s race or ethnicity, any medications they are taking currently or have taken recently, any exposure to harmful substances, any family history of disease, where they work, any recent travels, and risk factors for infections that target the immune system. They may get these types of infections if they are on medications that suppress the immune system or if they have the human immunodeficiency virus (HIV). Cases like recent travel to places where certain diseases are common can give doctors a hint about what is causing the patient’s symptoms. For example, Histoplasmosis and Schistosomiasis are two diseases that could potentially cause hepatic granulomas. Histoplasmosis usually takes care of itself, but in some people, like infants or those with conditions that weaken the immune system, it can become a chronic, widespread disease. Patients with this condition often have an enlarged liver (62% of cases) or abnormal liver tests (84% of cases). Schistosomiasis, on the other hand, is known for causing progressive scarring in the liver called “pipestem fibrosis”, an enlarged spleen, and bleeding varicose veins.
Testing for Granulomatous Hepatitis
If your doctor suspects you have granulomatous hepatitis, a condition where clusters of immune cells form in your liver, they might conduct a variety of tests. These can include blood tests to examine your red and white blood cell counts and inflammation levels, metabolic panels, checks for clotting ability, and tests for various infections and antibodies related to certain autoimmune diseases. They might also test for substances levels such as eosinophils and transaminases. Usually, transaminases, which are enzymes released when your liver is damaged, won’t be more than twice the normal limit.
Imaging tests like CT, MRI or ultrasonography are effective for visualizing the liver and identifying any lesions. A chest x-ray could also help identify potential causes of your illness, such as lymph nodes that enlarge in certain diseases. Positron Emission Tomography (PET scans) might be used more in the future, but are still being developed.
A biopsy, where a small piece of liver tissue is removed and examined, is a key tool in diagnosing this condition. However, it can be challenging to tell the cause of the problem just from this. It’s important to also test for things like fungi, bacteria, and other foreign bodies.
Sarcoidosis is a common cause of granulomatous hepatitis, especially in people of Scandinavian descent or African-Americans, and more often in women. It often leads to an enlargement of the liver and liver nodes. This disease sometimes increases the levels of angiotensin-converting enzyme and can result in a lower parathyroid hormone level. However, most patients with this condition do not show symptoms unless it gets more severe.
Primary biliary cholangitis, an autoimmune liver disease common in middle-aged women, is another common cause. In this disease, granulomas surround damaged bile ducts. Anti-mitochondrial antibodies are common and usually help diagnose this disease.
Tuberculosis (TB) and histoplasmosis are two infections that also commonly cause granulomatous hepatitis. TB granulomas might or might not be dramatically inflamed, depending on the type. These problems often cause reduced levels of albumin, a protein made by your liver, and sodium in the blood. Special stains and polymerase chain reaction (PCR) techniques are used to detect these infections.
Additionally, strains of the bacteria Mycobacterium bovis used in a tuberculosis vaccine known as BCG, are associated with this condition, especially in people with weakened immune systems. This can lead to serious complications including liver failure.
HIV patients can also get granulomatous hepatitis as a common side effect of the Mycobacterium avium complex (MAC) infection. Finally, certain medications can cause granulomatous hepatitis, and this determination is usually made by ruling out other possibilities.
Treatment Options for Granulomatous Hepatitis
When managing granulomatous hepatitis, a condition where clumps of cells form in the liver, it’s important to consider the underlying cause. In cases where symptoms are not present or the cause is unknown, regular check-ups and liver function tests might be sufficient. If symptoms are present but the cause is still unknown, corticosteroids, a type of medication that reduces inflammation, are often effective. However, it’s crucial to rule out tuberculosis before starting this type of treatment. Treatments including corticosteroids are usually gradually reduced over 4 to 8 weeks, but a second course may be necessary. Other drugs such as Methotrexate and Infliximab may be used when corticosteroids aren’t suitable. If a patient doesn’t respond to corticosteroids, further tests for unusual infections, lymphoma, and other cancers should be considered. Stopping exposure to any implicated drugs or toxins may lead to improved liver health.
Hepatic sarcoidosis, a rare type of liver disease, is treated on a case-by-case basis as some patients may not require specific treatment, while others may need therapy for their whole life. Like granulomatous hepatitis, corticosteroids are the typical first-line treatment, with other drugs such as Methotrexate, Chloroquine, Azathioprine, and Ursodeoxycholic acid used as secondary options. Only 5% of people with liver-involved sarcoidosis need treatment, although symptoms of portal hypertension, high blood pressure in the liver, may necessitate a liver transplant. This is rarely needed as most patients respond well to systemic therapy, treatment that affects the whole body rather than one area. However, caution is needed when using interferon therapy in those with both sarcoidosis and hepatitis C as it could lead to worsening symptoms or new symptoms.
Another therapeutic option, Ursodeoxycholic acid, can help to relieve itchy skin caused by sarcoidosis and PBC (primary biliary cholangitis) due to a type of jaundice. It has also been found to slow the progression of PBC, lead to improvements on a microscopic level, and improve survival rate. For those patients who do need a liver transplant due to PBC, the prognosis is very positive, with over 90% surviving at least a year.
If granulomas have occurred due to infection, appropriate antibiotic therapy is necessary. In the case of tuberculosis-associated granulomas, rifampin, isoniazid, pyrazinamide, and ethambutol are the typical treatment. For fungal infections like histoplasmosis and coccidioidomycosis, antifungals like amphotericin or flucytosine are used. Isoniazid may cause liver injury, so regular liver and kidney function tests are needed. It should also be combined with pyridoxine to prevent nerve damage. A similar regimen is used to treat infections associated with BCG, a vaccine for tuberculosis, except it isn’t combined with pyrazinamide.
What else can Granulomatous Hepatitis be?
Granulomatous hepatitis can be caused by several different factors, making it a bit tricky to diagnose. It could be due to unusual infections, certain types of cancers like lymphoma, or solid organ cancers, such as kidney cancer. A correct diagnosis requires careful examination and consideration of these possibilities.
What to expect with Granulomatous Hepatitis
Granulomas, which are small areas of inflammation, can often improve with the right treatment, especially if they were caused by medication or infection. In the case of sarcoidosis, a disease that causes granulomas, they might even get better on their own. However, they can also last a long time, cause no symptoms, or lead to serious liver issues like fibrosis, portal hypertension, or cirrhosis.
A treatment involving ursodeoxycholic acid has been found to slow down the progression of a liver disease called PBC, and leads to improvements in the structure of the liver tissue. It also boosts survival rates and reduces the need for a liver transplant. But if a transplant does become necessary, the survival rate after a year is usually over 90%, indicating excellent outcomes.
Possible Complications When Diagnosed with Granulomatous Hepatitis
Granulomatous hepatitis, a type of liver inflammation, can lead to scarring, increased blood pressure in the liver, or liver cirrhosis (damage), depending on how severe it is and what’s causing it. Quick and suitable treatment is crucial to stop this from progressing to serious liver issues or life-threatening infections. In some situations, treatment may need to continue indefinitely.
Preventing Granulomatous Hepatitis
Granulomatous hepatitis involves the appearance of small, round areas of inflammation, known as granulomas, in the liver. Granulomas usually form as a response to various harmful factors. Patients should be informed that these granulomas may not cause any symptoms and can be discovered by accident or in connection to another, broader health condition. The granulomas might shrink with proper treatment, or they may stay the same size for years without causing symptoms. Either way, patients should keep in regular contact with their healthcare providers to monitor their condition.
